Targeting Extracellular Bacterial Proteases for the Development of Novel Antivirulence Agents

As resistance to clinically available antibiotics persistently increases, applying new strategies to target pathogenic bacteria are paramount to design effective drugs. Bacterial proteases play vital roles in cell viability and stress response, contributing to the pathogenicity of the resistant bacteria. Targeting these extracellular enzymes by antivirulence therapy is a prominent strategy in combating multi-drug resistant bacteria. By preventing the colonization and infiltration of the host, this method can lower selection pressure and reduce resistance development significantly. Here, we review the role of bacterial proteases, the rise of antivirulence therapy and we report on the development of novel antivirulence agents targeting two key virulence factors: elastase B (LasB) from Pseudomonas aeruginosa and collagenase H (ColH) from Clostridium histolyticum.